Dr. Robert H. E. Hudson Profile

Dr. Robert H. E. Hudson

at Western Univ Canada

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Publications (2)

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Proceedings Article | 29 March 2016 Paper

Evaluation of 6-([18F] fluoroacetamido)-1-hexanoic-anilide (18F-FAHA) as imaging probe in tumor xenograft mice model

Fiona Li, Sung Ju Cho, Lihai Yu, Robert H. Hudson, Leonard Luyt, Christopher Pin, Michael Kovacs, James Koropatnick, Ting-Yim Lee

Proceedings Volume 9788, 978814 (2016) https://doi.org/10.1117/12.2216905

KEYWORDS: Positron emission tomography, Image analysis, Modeling, Cancer, Melanoma, Mouse models, Oncology, Breast, Tumors, Medical research, Data modeling, Tissues

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Alteration in genetic expression is as important as gene mutation in cancer development and proliferation. Epigenetic changes affect gene expression without altering the DNA sequence. Histone deacetylase (HDAC), an enzyme facilitating histone remodelling, can lead to silencing of tumor suppressor genes making HDAC inhibitors viable anticancer drugs against tumors with increased activity of the enzyme. In this study we evaluated ¹⁸F-fluroacetamido-1-hexanoicanilide (¹⁸F-FAHA), an artificial HDAC substrate, as imaging probe of HDAC activity of human tumor xenografts in immunocompromised host mice. Human breast and melanoma cell lines, MDA-MB-468 and MDA-MB-435 respectively, known to overexpress HDAC activity were xenografted into immunocompromised mice and HDAC activity was imaged using ¹⁸F-FAHA. The melanoma group was treated with saline, SAHA (suberoylanilide hydroxamic acid, an approved anticancer HDAC inhibitor) in DMSO, or DMSO as positive control. Tracer kinetic modelling and SUV were used to estimate HDAC activity from dynamic PET data. Both breast tumor and melanoma group showed great variability in binding rate constant (BRC) of ¹⁸F-FAHA suggesting highly variable inter- and intra-tumoral HDAC activity. For the SAHA treated melanoma group, HDAC activity, as monitored by BRC of ¹⁸F-FAHA, decreased more than the two (positive and negative) control groups but not tumor growth. Our preliminary study showed that noninvasive PET imaging with ¹⁸F-FAHA has the potential to identify patients for whom treatment with HDAC inhibitors are appropriate, to assess the effectiveness of that treatment as an early marker of target reduction, and also eliminate the need for invasive tissue biopsy to individualize treatment.

Proceedings Article | 13 October 2005 Paper

New fluorescent nucleobases derived From 5-alkynylpyrimidines

Robert Hudson, Andrew Dambenieks, Joanne Moszynski

Proceedings Volume 5969, 59690J (2005) https://doi.org/10.1117/12.629808

KEYWORDS: Luminescence, Solids, Analog electronics, Carbon monoxide, Chromophores, Chlorine, Chemistry, Molecules, Crystals, Nitrogen

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Fluorescent reporter groups are widely used in many areas of macromolecular science. In nucleic acid chemistry, fluorescently labeled oligonucleotides find use in the study of nucleic acid conformations, as reporters of the state of hybridization and as probes of nucleic acid-protein interactions, as well as, probes and primers for the detection and quantification of desired sequences. Often, the fluorophore is a separate and independent entity covalently attached to an otherwise unmodified oligonucleotide. Another class of fluorophore is the nucleobase analog - a chemically modified nucleobase that is unable to base pair properly. Recently, we have become interested in pyrrolocytosine (pC) as an intrinsically fluorescent, pairing-competent nucleobase. It has previously been shown that incorporation of pyrrolocytidine into oligonucleotides gives a fluorescent molecule that responds to the state of hybridization. We have refined the syntheses of pyrrolocytosine derivatives and the related modified uracil derivatives, furanouracil (fU), from cytosine and uracil respectively via three sequential steps: iodination of the nucleobase; Pd-catalyzed cross-coupling with a terminal alkyne; and metal-catalyzed cyclization. The fluorescence properties of the 5-alkynyl nucleobases and the bicyclic pC and fU analogs have been characterized and depend on: 1) the nature of the substituent on the alkyne, 2) whether the nucleobase is 5-alkynyl or cyclized, and 3) the presence of a substituent on the N¹-position of the nucleobase. The chemistry and properties of peptide nucleic acid oligomers incorporating these types of base modifications and their possible use in point-mutation detection is presented.

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